The advantage of outsourcing development and manufacturing services is that it allows pharma companies to focus on their core business, such as R&D and marketing, which can crucially reduce costs, time-to-market, and risk. Contract Pharma talks with leaders at several CDMOs about current trends in outsourcing and the importance of investment in CDMO partnerships in today’s pharma landscape.

Contract Pharma: How have outsourcing relationships evolved over the last 10 years?

Claire Madden-Smith, senior vice president, Juniper Pharma Services: The last decade has seen a paradigm shift in outsourcing relationships. Where once outsourcing was driven largely by a desire to reduce costs of routine or commodity based activities, today we see additional factors such as technical expertise, improved operational efficiency, access to innovation and risk management being equal or primary drivers towards outsourcing. With the resurgent investment in biotech development over the last five years, the relationship between sponsor and vendor has become much more collaborative.

Colin Mackay, founder and chief executive officer, Symbiosis: There has been significant consolidation in the contract manufacturing sector, meaning the industry is less fragmented with fewer bigger service providers. This reduces the choices available to drug developers when selecting partners to work with to develop their promising molecules. As a result, relationships seem to be a lot more about strategic partnerships and less about straightforward operational outsourcing.
Symbiosis has proactively nurtured relationships with many small biotechs and specialty pharma companies who are looking for a partner that they can grow with. As such, the cultural fit with their chosen CMO is as important as technical capabilities and levels of compliance, which may not have been where the emphasis was placed 10 years ago.

Anthony Sheehan, chief executive officer, Saneca Pharma: We have seen many pharmaceutical companies redefine their offering and sell off parts of their business in order to allow their in-house resources to focus on core business areas where they have the most success. By outsourcing additional services according to customer demand, companies have been able to make huge cost and time savings. In fact, Saneca Pharma was born out of this type of divestment and has a big pharma heritage, having previously existed as a Sanofi site.

This trend has had a positive effect on CDMOs who are seeing a higher demand for a broader range of outsourced services to plug the gaps in their customers’ in-house capacity. As a result, many CDMOs are expanding their offering to become full-service providers that can offer a wider variety of capabilities in order to remain competitive. While smaller, niche service providers will continue to exist, there is an increased focus on developing ‘true partnerships’ with CDMOs that are able to provide a multitude of services. When a CDMO can do this from one single site this helps to further streamline the supply chain for its customers.

Mark Quick, executive vice president, corporate development, Recipharm: Outsourcing relationships are now much more strategic. The decision to outsource is made at an earlier stage in a product’s development, rather than being used as a backup when things go wrong, or when resources get stretched. Consequently, long-term partnerships are becoming more commonplace. The growing financial pressures placed on pharmaceutical companies is one reason for this shift, as they look to make cost and time savings by outsourcing to CDMOs with specialist capabilities. This, together with a number of CMO failures, has led to companies more stringently evaluating contract partners. Companies with strong compliance track records and a good financial history tend to fair better with this scrutiny.

Manuel Leal, business development director, Idifarma: The outsourcing industry continues to grow. The increasing importance of generics, which has driven competition in the pharmaceutical sector generally, has led to a significant increase in outsourcing, mostly when specific capabilities like high potency or small-scale manufacturing are required. Customers now expect increased flexibility and the ability to adapt to products with special demands in terms of manufacturing conditions, available technologies, smaller volumes, global distribution, etc. Also, the service level demands have increased and customers want better response times from trusted CDMOs, without compromising the highest quality standards.

CP: In your opinion, what does it take to maintain an effective sponsor-partner relationship?

Madden-Smith: In my experience, the most effective relationships are those built on a shared understanding of the primary end goals and assumptions. Effective communication on all sides, working together as a single team and continuously checking assumptions is paramount to keep the drug development activities on the most efficient track towards a successful and robust product.

Mackay: CMOs need to invest in building a successful relationship with each client based on a clear understanding of a specific clients’ definition of an ideal outcome. Only then can a true partnership begin to be established.

If you are a smaller, specialist CMO like Symbiosis, we need to demonstrate how we are best placed to overcome specific challenges that a customer may encounter and offer a niche competitive strength, which our competitors can’t. For example, while larger CMOs offer relatively fixed service offerings, as a small-scale sterile manufacturer, we have the operational flexibility to meet tight timescales and tailor our services directly and specifically in response to a clients’ requirements. So, if time is of the essence, our agility and speed of delivery resonates strongly with our clients.

In terms of maintaining a relationship, an organization will only have a relationship to be concerned about if it started out with its eyes and ears open, and with an intention to build a relationship, which is a long-term one. Generally speaking, those organizations who focus on volume, or are naturally transactional in their dealings with customers, tend to concern themselves less with the issue of maintaining relationships. Our small-to-medium clients don’t see value in that approach.

Sheehan: It’s critically important to fully understand your customer and their expectations. Underestimating the scope of a contract and failing to deliver will have a lasting effect on sponsor-partner relationships. Taking the time to fully comprehend the challenges your customer is facing is vital to maintaining a strong partnership. For example, Saneca Pharma works with many pharmaceutical companies who not only value technical capabilities and expertise, but also flexibility and open communication, meaning it’s important our teams are responsive and can adapt to changing requirements. In a densely populated market, a quality service offering combined with a broad portfolio of capabilities to provide the agility needed in this fast-moving sector can really help CDMOs to stand out.

Quick: The answer here is not rocket science. You need to provide customers with the services they want and deliver what you say you will. Of course, cost is always a factor in any outsourcing decision, so providing good value for money is also important. The ability to manage complexity is also fundamental to an effective relationship. Our customers come to us for guidance on development and manufacturing challenges and it is our job to manage these on their behalf, removing the headache. A focus on innovation is the only way to make this happen; you need to improve and innovate all the time, whether this is to overcome complex formulation challenges, reduce lead times during manufacturing or minimize cost. Those CDMOs that provide a full-service offering are best placed to offer a turnkey solution to customer challenges and therefore build effective, long-term relationships.

Leal: We look for long-term strategic collaborations with clients. We always strive to integrate with customers through a client-centric approach to build mutual trust and transparency. This trust is often generated in complex moments within a project so it’s essential to be upfront with the client, dedicating time to the clear definition of roles and expectations at the outset, as well as being proactive when solving technical challenges.

CP: What should pharmaceutical companies be considering when choosing an outsourced partner?

Madden-Smith: By the very nature of dealing with the unknowns of new chemical entities, drug development has many twists and turns which need careful navigation and require different expertise sets at different stages. Obviously, compliance records, costs and expertise are important but most companies will look competitive in these areas, so it is important to think more strategically.

In the CDMO world, when a pharmaceutical company is considering an outsource partner they should have considered what their success looks like long term and be planning for achieving that best chance of success. Starting with the finish in mind, enables the foundational concepts around a target product profile to be produced, which acts as an excellent guide to the enormity or simplicity of the task at hand. The consideration should then be around whether a generalist outsourcing partner will suffice or whether specific areas of expertise are critical to product development success.

Based on this type of approach it is possible to then be specific in the analysis of which CDMOs or even multiple CDMOs best fit the need. That is, if you have a challenging molecule with a high risk of failing to achieve relevant bioavailability, it would make no sense to focus on a great CMO, if they lack innovative expertise in early formulation development phases. Likewise, if you have a challenging timeline you would want to consider which company can be most nimble to respond whilst still providing expertise in development of a robust validated product.

However, where the product development follows a more conventional path, then a generalist CDMO offering cost effective development will clearly suffice. This type of risk-based approach would hopefully avoid costly mistakes of either under or over estimating the criticality of each development step.

Mackay: Regulatory compliance, technical capability and operational flexibility are core client service expectations that we believe need to be demonstrated in today’s competitive environment.

As mentioned, we believe that cultural fit is also fundamentally important. We ideally partner with dynamic, fast-growing companies, who are pragmatic yet focused on achieving the core project objectives. Smaller drug developers are more likely to want to partner with smaller CMOs that will value their business and offer real experience to help them navigate the drug development landscape. We’ve heard time and time again from smaller drug developers that they don’t like to feel like a little fish in a very large pond, which is often the case when using a larger, one-stop-shop style CDMO.

Sheehan: As a result of the supply chain efficiencies, such as reduced lead times and cost savings, that can be gained from using a single supplier, it’s becoming increasingly common for pharmaceutical companies to seek a turnkey service from CDMOs to support taking their products through the entire product lifecycle. The broader the scope of services your CDMO can offer the better, particularly if you’re looking to develop a long-term partnership. A wider service offering could meet the requirements of future products too and mitigate the task of finding a new, reputable CDMO for each project. In addition to a breadth of services and technologies, your contract partner should also have a responsive and experienced team that can help to overcome development, manufacturing and distribution challenges as well as adding genuine value to your operations.

Quick: Firstly, due to the nature of our industry, quality standards and compliance culture are key. Pharmaceutical companies should also consider the range and breadth of services offered by a contract partner and its geographic reach, as ultimately, this will help to simplify and streamline their supply chain. At present, the greatest challenge faced by CMOs is the upcoming deadlines for pharmaceutical serialization in the U.S. and Europe. When choosing an outsourced partner, it’s important to assess its serialization program and how prepared it is to meet the 2017 and 2019 compliance requirements. There is a likelihood that many CMOs will not be ready to supply serialized drug products and this will have a serious impact on product supply into key markets.

Leal: Besides the required technical capabilities, it’s important pharmaceutical companies choose a partner that is client-orientated—having the customer as the ‘end goal’ and not just as a means to other objectives. It also takes long-term focus, a clear and well-defined business model and the avoidance of conflicts of interest, which inevitably appear if the CDMO has its own product portfolio, for instance.

Alignment and integration with the customer as well as reliability, responsiveness and flexibility remain very important factors for long-term success.

CP: In which areas of drug development and manufacturing are you seeing the greatest demand for outsourcing?

Madden-Smith: In general, the CDMO sector across the board has seen considerable annual growth over the past five years. Specifically, at Juniper we have seen an increased outsourcing tendency for preclinical and early Phase I and II development activities where there are challenges around small molecule APIs, for example poorly water-soluble drugs. Clients are increasingly coming to CDMOs that can bring a breadth and depth of expertise to the development and manufacture of dosage forms, to deal with significant technical challenges.

Mackay: We have experienced significant growth in the U.S. market in recent years, with the North American market now accounting for over a third of our revenues. We expect that to continue as demand from U.S.-based biotechnology firms looking for small scale aseptic manufacturing capabilities to support clinical trials increases in line with their collective financial good health.

However, with a shift towards the development of personalized medicines among emerging biotech and pharma companies and a greater need for cytotoxic products, there will be a greater need than ever before for specialist CMOs that can rapidly manufacture small (and potentially complicated) batches for small patient populations.

Sheehan: There is growing demand for controlled release technologies that can optimize the performance of novel and existing drugs by reducing the potency of a product or the risk of dose dumping and adverse side effects. Given the level of skill and technical expertise required to develop and manufacture controlled release dosage forms, pharmaceutical companies are increasingly asking their CDMOs for these services. CDMOs with years of expertise in this area can help drug manufacturers to speed-up time to market and reduce the overall cost of developing and manufacturing drugs in this way. There is also growing demand for controlled substances, which require specialist facilities and in some cases controlled release technology. Our site was originally established in 1941 to produce morphine active pharmaceutical ingredient (API) and controlled substances in API and finished dosage form (FDF), which is still a focus area for Saneca Pharma today.

Quick: This very much depends on the type of customer. While big pharma may use CDMOs for greater flexibility and efficiency throughout the drug development lifecycle, smaller companies, including the growing number of virtual pharma firms, rely on contract partners to access specific specialist services, expertise or manufacturing capacity that they do not have in-house. Outsourcing is particularly prevalent in areas where specialist technology and expertise is required, so we are experiencing increasing demand for our development services. This is particularly the case in areas including formulation development, clinical supply manufacture and trial management to achieve first in human milestones, as well as chemistry services.

In terms of manufacturing, the greatest demand remains in the production of solid dosage forms, representing more than 47 percent of the CDMO market. However, the manufacture of injectables is set to rise and reach 46 percent of the market share by 2020. This is directly related to the increasing development of cytotoxic drugs and biologics.

Leal: There are many opportunities in specialized or niche contract manufacturing. The capacity to handle highly potent compounds and the flexibility to manufacture small-scale batches are becoming very important for many of our customers and products. The availability of innovative technological platforms able to improve cost and process efficiencies, product safety and bioavailability or patient compliance also constitute a number of growth opportunities.

CP: How do you see the future of outsourcing and what will the impact be on current sponsor-partner relationships?

Madden-Smith: The outsourcing trend looks set to continue for the foreseeable future and we are seeing more long-term strategic relationships building where, not only is there a technical fit but also a strong cultural fit between sponsor and partner.

Mackay: We envisage the outsourcing sector to continue to grow steadily and it is showing no signs of slowing down. In a recent industry survey, the OSP William Reed State of the Industry report 2017, 44 percent of pharmaceutical companies surveyed said they expect to outsource more business this year than last, which is interesting market feedback.
We therefore expect this trend to continue, with growth in the parenteral manufacturing space coming from biopharma companies as they continue to progress new drug products to market, significantly driven by an increase in industry funding.

While many CMOs continue to expand their offerings, there will continue to be demand for niche manufacturing services from specialist providers that can offer the flexibility needed to meet increasingly tight timescales in the drug development pipeline.

Success in outsourcing is underpinned by technical capabilities and effective communication in the sponsor-partner relationship. As a result, we expect to see more and more clients moving away from tactical outsourcing initiatives in favor of a relationship-oriented strategic partnership with CMO partners across a collaborative supply chain.

Sheehan: It is likely that the CDMO landscape will continue evolve, perhaps at a slightly slower pace, further changing the relationship between contract partners and their customers. New and more challenging drugs entering the supply chain will continue to drive the demand for comprehensive development services, particularly controlled release technologies. There will continue to be demand for competitive pricing, without compromising on quality. Whereas in the past companies have looked to Eastern countries, such as India, to generate these savings, increasing concerns surrounding the quality of drugs produced in this market means more and more pharmaceutical companies are keen to move their operations back to Europe. With this in mind, full-service CDMOs in lower cost markets such as Slovakia will find themselves ideally placed to deliver a service that combines cost effectiveness, quality, technical expertise and speed-to-market.

Quick: Ongoing transformations in the pharmaceutical industry, including pricing pressures, more stringent regulation, modernization and market complexities, are all driving demand for outsourcing and we expect this to continue in the years to come. As the population continues to age and we see higher incidence of lifestyle and chronic ailments, demand for innovation and new drug development will grow too. As the CDMO space is subject to more and more consolidation, we expect that pharmaceutical companies will begin to work with a smaller number of contract partners that are able to deliver a wider range of services. This will help to simplify the supply chain, enable the development of closer, more strategic relationships and ultimately, speed up new drugs to market. Pharma companies will continue to rationalize their manufacturing footprint and focus on their core business, while more virtual companies will appear with limited infrastructure. Both of these trends will help to feed CDMO pipelines and allow the outsourcing sector to grow. Pharmaceutical demand in emerging markets is also expected to increase between eight and nine percent per annum until 2020 and pharmaceutical companies will naturally evaluate CDMOs in terms of location/ proximity to market, labor cost and the ability to meet variable demand.

Leal: The higher efficiency of the outsourcing model in the pharma industry will lead to sustained growth, helped by factors such as the need for higher specialization. There is still room for improvement though: it is necessary for all parties involved to move from tactical collaborations to real strategic partnerships and then to client-supplier integration in order to be totally flexible and fully exploit the potential of outsourcing. This will help products keep competitive in the market while complying with the growing regulatory requirements.